The prevention of childhood obesity is an urgent public health priority. The Centers for Disease Control and Prevention reported that 17% of children and adolescents in the US had obesity in 2012, and children with obesity may experience higher lifetime risks of age-specific morbidity and mortality. Environmental exposures in early life may promote the development of obesity and related adverse cardio-metabolic outcomes in children. Specifically, maternal exposure to particulate and gaseous air pollutants during pregnancy may lead to programming of offspring adiposity and altered postnatal growth trajectories. Previous epidemiologic studies have identified associations between air pollution exposure and childhood overweight or obesity, but have rarely looked at exposures in the prenatal period, or measured biological factors in the mother or infant that could mediate the observed relationship. The proposed research is an in-depth evaluation of the role that prenatal exposure to traffic-related air pollution may play in offspring adiposity and early childhood overweight and obesity, considering as mediators both inflammatory markers in maternal and umbilical cord blood, and epigenetic markers of DNA methylation in umbilical cord blood. The overall aim of this Career Development Award is to advance the candidate into an independent research career in environmental epidemiology, with an emphasis on the long-term health effects of exposure to environmental toxicants during the prenatal period. The analytical skills acquired during the mentored training period of this award will include the use of geographic information systems-based methods of spatial exposure assessment and modeling, the implementation of advanced statistical methods to evaluate possible causal mediation, and the analysis and interpretation of epigenetic markers in epidemiologic studies. These skills will be developed through mentored independent study, course work, and collaboration with experienced faculty in the fields of Epidemiology, Geography and Environmental Sciences, Atmospheric Science, Genetics and Genomics, and Biostatistics and Informatics. The candidate will use spatial modeling methods to estimate residential exposure to traffic-related air pollution during pregnancy in an existing longitudinal pre-birth cohort study focused on the developmental origins of obesity and related cardio-metabolic disorders. Stored maternal and umbilical cord serum samples will be analyzed for markers of systemic inflammation, which may be linked to traffic-related air pollution exposure and also to offspring risk for overweight and obesity. During the independent period of the award, the candidate will use the exposure assessment developed in the mentored period to estimate associations between prenatal exposure to traffic-related air pollution and offspring adiposity and obesity. Maternal and fetal systemic inflammation and offspring DNA methylation in umbilical cord blood will be investigated as possible mediators of the association. The project will make a substantial contribution to the field of air pollution epidemiology and the early-life environmental factors that influence childhood obesity risk.